Thioridazine - instructions for use, dosage, side effects, contraindications

Has antipsychotic, tranquilizing, antidepressant, antipruritic and antiemetic effect. The mechanism of antipsychotic action is due to the blockade of postsynaptic dopamine receptors in the mesolimbic structures of the brain. The central antiemetic effect is due to oppression or blockade of dopamine D₂receptors in the chemoreceptor trigger zone of the brainstem, peripheral by the blockade of the vagus nerve in the digestive tract. Also possesses α-adrenoblocking and m-holinoblocking action. The blockade of histamine H1 receptors and m-cholinergic receptors is most pronounced among all neuroleptics. In small doses, it has an anxiolytic effect, reduces feelings of tension and anxiety, and exhibits antipsychotic (neuroleptic) properties in higher doses.

Pharmacokinetics:

Absorption is high. Biotransformation in the liver (CYP1A2, 2D6) with the formation of an active metabolite - mesoridazine; inhibitor - CYP2D6. The half-life is21-25 hours

Indications:

Schizophrenia (as a drug of the second line of therapy in patients who are contraindicated in other drugs, or there is no curative effect when taking other medicines).

Psychotic disorders, accompanied by hyperreactivity and excitement.

Severe behavioral disorders associated with aggressiveness, incapacity for prolonged concentration of attention.

Psychomotor agitation of various genesis.

Neuroses accompanied by fear, anxiety, psychomotor agitation, psychoemotional stress, sleep disorders, obsessive states, depressive disorders.

Abstinence syndrome (substance abuse, alcoholism).

In children's psychiatry apply for behavioral disorders with increased psychomotor activity.

ICD-10

V.F20-F29.F20 Schizophrenia

V.F20-F29.F21 Chrysotile disorder

V.F20-F29.F22 Chronic delusional disorders

V.F20-F29.F25 Schizoaffective disorder

V.F20-F29.F29 Inorganic psychosis, unspecified

V.F40-F48.F41.2 Mixed anxiety and depressive disorder

V.F40-F48.F42.9 Obsessive-compulsive disorder, unspecified

V.F40-F48.F48.0 Neurasthenia

V.F50-F59.F51.2 Sleep and wakefulness disorder inorganic etiology

V.F90-F98.F90.0 Violation of activity and attention

Contraindications:

Hypersensitivity, severe cardiovascular diseases (decompensated chronic heart failure, arterial hypotension), severe CNS depression and coma of any etiology, head trauma, progressive systemic diseases of the brain and spinal cord, pregnancy, breast-feeding, children's age (up to two years).

Carefully:

Alcoholism, pathological changes in the blood, breast cancer, zakratougolnaya glaucoma, prostate hyperplasia, hepatic and / or renal failure, gastric and duodenal ulcer (period of exacerbation), diseases accompanied by an increased risk of thromboembolic complications, epilepsy, myxedema, chronic diseases, accompanied by respiratory failure (especially in children), Reye's syndrome (increased risk of hepatotoxicity in children and adolescents), cachexia, vomiting, and advanced age.

Pregnancy and lactation:

In pregnancy, the use of the drug is only possible if the expected benefit to the mother exceeds the potential risk to the fetus. Adequate and well-controlled studies of drug safety during pregnancy have not been conducted.

If it is necessary to prescribe the drug during lactation, breastfeeding should be discontinued.

Recommendations FDA category C.

Dosing and Administration:In acute psychosis, mania and agitation depression in outpatient conditions, 150-400 mg per day are used, in the hospital - 250-800 mg per day (the average dose is 486 mg per day, the maximum dose is 800 mg per day).
With mild mental and emotional disorders - 30-75 mg per day, with moderate disorders - 50-200 mg per day.
Use in children with schizophrenia: inside. Up to 2 years: dose not established. 2-12 years: 10-25 mg 2-3 times a day; maintenance dose - 2.5-3 mg / kg or 7.5 mg / m² 3-4 times a day. 12 years and older: 50-100 mg 1-3 times a day; maintenance dose - 50-200 mg 2-4 times a day.

Side effects:

From the side CNS: confusion, late dyskinesias, agitation, agitation, insomnia, extrapyramidal and dystonic disorders, parkinsonism, emotional disorders, thermoregulatory disorders,decreased convulsive threshold, syncope, malignant neuroleptic syndrome.

From the side digestive system: sialoschesis, anorexia, increased appetite, indigestion, nausea, vomiting, diarrhea, paralytic ileus, hypertrophy of the papillae of the language, cholestatic hepatitis.

From the side of cardio-vascular system: decreased blood pressure, tachycardia, ECG changes, including dose-dependent lengthening of the QT interval, pirouette tachycardia.

From the side hematopoiesis system: agranulocytosis, leukopenia, granulocytopenia, eosinophilia, thrombocytopenia, aplastic anemia, pancytopenia.

Allergic reactions: allergic skin reactions, erythema, rash, exfoliative dermatitis, angioedema, bronchospastic syndrome, nasal congestion, photophobia.

From the side genitourinary system: decreased libido, ejaculation disorder, dysmenorrhea, hyperprolactinemia, gynecomastia, paradoxical ischuria, dysuria, priapism.

From the side endocrine system: false positive pregnancy tests, weight gain.

From the side sense organs: visual impairment, photophobia.

Other: melanosis of the skin (with prolonged use in high doses).

Overdose:

Symptoms

From the side of cardio-vascular system: arrhythmias, decreased blood pressure, shock, changes in ECG, prolongation of QT and PR intervals, nonspecific changes in ST segment and T wave, bradycardia, sinus angina, atrioventricular block, ventricular tachycardia, ventricular fibrillation, pirouette tachycardia, myocardial dysfunction.

From the side CNS: sedative effect, extrapyramidal disorders, confusion, agitation, hypothermia, hyperthermia, convulsions, areflexia, coma.

From the side autonomic nervous system: mydriasis, miosis, dry skin and mucous membranes of the oral cavity, nasal congestion, urinary retention, blurred vision.

From the side respiratory system: respiratory depression, apnea, pulmonary edema.

From the side digestive system: decreased motility, constipation, intestinal obstruction.

From the side urinary system: oliguria, uremia.

Toxicity begins to manifest with a concentration of thioridazine in the plasma of more than 10 mg / l, at a concentration of 20-80 mg / l, death occurs.

Treatment

It is necessary to provide airway patency and establish adequate oxygenation and pulmonary ventilation.Immediately begin a long-term monitoring of cardiovascular activity (ECG). Treatment consists of correction of electrolyte disturbances and acid-base balance, the introduction of lidocaine (caution is recommended due to an increased risk of seizures), phenytoin, isoproterenol, up to the installation of artificial pacemakers and defibrillation. In view of the possible additional prolongation of the QT interval, the use of disopyramide, procainamide and quinidine should be avoided. Correction of a lowered blood pressure may require the introduction of infusion solutions and vasopressors. With a persistently low blood pressure, the administration of phenylephrine, norepinephrine or metamyramine is indicated. Alpha-adrenoblocking properties of phenothiazine derivatives do not allow the use of nonselective alpha and beta-adrenomimetics (epinephrine, dopamine) - the risk of paradoxical vasodilation.

To remove unabsorbed dose of the drug, it is recommended to wash the stomach using activated charcoal. Induction of vomiting is less preferable because of the risk of dystopia and potential aspiration of emetics.

Acute extrapyramidal disorders are treated with diphenhydramine or trihexyphenidyl.

When arresting seizures, barbiturates should be avoided (risk of aggravation of respiratory depression).

Due to the high volume of distribution and strong binding to plasma proteins, forced diuresis, hemoperfusion, hemodialysis and pH change of urine most likely do not affect the excretion of phenothiazine derivatives from the body.

Interaction:

Synergism of action with general anesthetics, narcotic analgesics, barbiturates, ethanol, atropine.

Enhances the hepatotoxic effect of hypoglycemic agents. With amphetamine - it acts antagonistically.

With levodopa - reduces antiparkinsonian action.

Use with epinephrine can lead to a sudden and pronounced decrease in blood pressure.

With guanethidine - reduces the antihypertensive effect of the latter, but enhances the effect of other antihypertensive drugs, which increases the risk of significant orthostatic hypotension.

Reduces the effect of anticoagulants.

The action of thioridazine can weaken anticonvulsant drugs, cimetidine.

Quinidine potentiates cardiodepressant action.

Ephedrine contributes to a paradoxical decrease in blood pressure.

Sympathomimetics intensify arrhythmogenic action.

Probucol, astemizole, cisapride, disopyramide, erythromycin, pimozide, procainamide and quinidine contribute to an additional elongation of the QT interval, which increases the risk of developing ventricular tachycardia.

Antithyroid drugs increase the risk of agranulocytosis.

Reduces the effect of funds that reduce appetite (with the exception of fenfluramine).

Reduces the effectiveness of the emetic action of apomorphine, enhances its inhibitory effect on the central nervous system.

Increases the concentration in the plasma of prolactin and prevents the action of bromocriptine.

When used simultaneously with tricyclic antidepressants, maprotiline, MAO inhibitors, histamine H1 receptor blockers, lengthening and strengthening of sedative and m-cholinoblocking effects is possible.

With thiazide diuretics - increased hyponatremia.

With drugs lithium - reduced absorption in the gastrointestinal tract, increasing the rate of excretion by the kidneys of lithium ions, increased severity of extrapyramidal disorders, early signs of lithium toxicity (nausea and vomiting) can be masked antiemetic effect thioridazine.

In combination with beta-blockers enhances the hypotensive effect, it increases the risk of irreversible retinopathy, arrhythmias and tardive dyskinesia.

Interaction with drugs extending the QT interval (cisapride) and inhibitors of the isoenzyme CYP2D6 (fluoxetine, paroxetine), can contribute to the occurrence of arrhythmias, including pirouette tachycardia.

When interacting with fluvoxamine, propranolol, pindolol, thioridazine in the blood plasma can increase, which increases the risk of arrhythmias.

Special instructions:

There is no information on the effectiveness of thioridazine in the treatment of dementia. Its use in such patients leads to the manifestation of adverse reactions and anxiety.

In the treatment of schizophrenia in elderly patients thioridazine is equal in effectiveness to other antipsychotics, but long-term studies of good quality are required. The incidence of undesirable drug reactions with thioridazine is lower than with other neuroleptics.

Thioridazine is more effective in the treatment of alcohol withdrawal syndrome than chlordiazepoxide.

In the treatment of schizophrenia thioridazine shows fewer side effects than chlorpromazine and trifluoperazine.

Instructions

Thioridazine (Thioridazinum)